DOCSLIB.ORG

Nibs: Protein Kinase Inhibitors Kinase Protein Nibs: Formats

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Nibs: Protein Kinase Inhibitors Protein kinases are one of the most important categories of targets in oncology and drug discovery in today’s research because of their key roles in the pathogenesis of many illnesses due to mutations, overexpression, and dysregulation of these enzymes. Over the past 20 years, tremendous progress has been made in developing drugs against protein kinase family of enzymes. So far, the U.S. FDA has approved >52 Protein kinase inhibitors as drugs. Of the 52 approved drugs, 43 have suffix “nib” in their names. The suffix “nib” indicates a small-molecule inhibitor (“nib” is verbal shorthand for “inhibit”) of kinase enzymes. More specifically, “tinib” is used for tyrosine kinase inhibitors, “anib” for angiogenesis inhibitors, and “rafenib” for rapidly accelerated fibrosarcoma (RAF) kinase inhibitors. BioVision offers >120 structurally diverse “nibs” for research. Many of these nibs are also available as “ready-to-use” “EZSolution” formats. Product Name Cat. No. Size CAS. No. Known Targets Acalabrutinib B1193 5 mg, 25 mg 1420477-60-6 Bruton's tyrosine kinase (BTK) Afatinib (BIBW2992) 1616 1 mg, 5 mg 439081-18-2 EGFR, ErbB2, ErbB4 Afuresertib hydrochloride B1848 5 mg, 25 mg 1047645-82-8 AKT Alectinib (CH5424802) 2867 5 mg, 25 mg 1256580-46-7 ALK and RET Allitinib B3002 1mg, 5mg 897383-62-9 ErbB2 and EGFR Alofanib B3009 5mg, 25mg 1612888-66-0 FGFR2 Alpelisib B1271 5 mg, 25 mg 1217486-61-7 PI3-K Altiratinib 9563 5 mg, 25 mg 1345847-93-9 MET, TIE2, VEGFR2 and TRK c-MET, c-RET and the mutant Amuvatinib 9458 5 mg, 25 mg 850879-09-3 forms of c-KIT, PDGFR & FLT3 Anlotinib, Free base B2156 5 mg, 25 mg 1058156-90-3 VEGFR, FGFR, PDGFR Apatinib Mesylate B1608 5 mg, 25 mg 1218779-75-9 VEGFR2 Apatinib, Free base B1613 5 mg, 25 mg 811803-05-1 VEGFR2 oncogenic KIT and PDGFRA Avapritinib B2999 1mg, 5mg 1703793-34-3 mutations Avitinib B2995 5mg, 25mg 1557267-42-1 EGFR Axitinib (AG-013736) 1581 5 mg, 25 mg 319460-85-0 VEGFR1/2/3, PDGFRβ Baricitinib 2842 10 mg, 50 mg 1187594-09-7 JAK1/2 EZSolution™ Baricitinib B2480 5 mg 1187594-09-7 JAK1/2 Baricitinib phosphate 2841 10 mg, 50 mg 1187595-84-1 JAK1/2 Belizatinib (TSR-011) B2028 5 mg, 25 mg 1357920-84-3 ALK, TRKA, TRKB, and TRKC Binimetinib (MEK-162) 2254 5 mg, 25 mg 606143-89-9 MEK1/2 Bosutinib (SKI-606) 1584 5 mg, 25 mg 380843-75-4 BCR-Abl, Src, Lyn, Hck Branebrutinib B2998 1mg, 5mg 1912445-55-6 Bruton's tyrosine kinase (BTK) www.biovision.com 155 S. Milpitas Blvd, Milpitas, CA 95035 T: 408-493-1800 F: 408-493-1801 Toll Free: 800-891-9699 (US Only) Product Name Cat. No. Size CAS. No. Known Targets Brigatinib (AP26113) 9675 5 mg, 25 mg 1197953-54-0 ALK, ROS1, IGF-1R, Flt3, EGFR Brigatinib Analog B2025 5 mg, 25 mg 1197958-12-5 ALK Brivanib B1325 1 mg, 5 mg 649735-46-6 VEGFR and FGFR Brivanib Alaninate B1326 1 mg, 5 mg 649735-63-7 VEGFR and FGFR Canertinib dihydrochloride(CI-1033, 1617 5 mg, 25 mg 289499-45-2 EGFR and ErbB2 PD-183805) Capmatinib B3005 5mg, 25mg 1029712-80-8 c-MET kinase RET, Met, VEGFR1/2/3, Kit, Carbozantinib 1935 5 mg, 25 mg 849217-68-1 TrkB, Flt3, Axl, Tie2, ROS1 Cediranib (AZD2171) 1613 1 mg, 5 mg 288383-20-0 VEGFR and c-Kit Ceritinib (LDK-378) B1928 5 mg, 25 mg 1032900-25-6 ALK, IGF-1R, InsR, ROS1 Cobimetinib B1689 5 mg, 25 mg 934660-93-2 MEK1/2 EZSolution™ Cobimetinib B2489 5 mg 934660-93-2 MEK1/2 Crenolanib 9679 5 mg, 25 mg 670220-88-9 FLT3 EZSolution™ Creolanib B2626 5 mg 670220-88-9 FLT3 ALK, c-Met (HGFR), ROS1, Crizotinib 1934 5 mg, 25 mg 877399-52-5 MST1R Dabrafenib mesylate 2800 5 mg, 25 mg 1195768-06-9 B-Raf (GSK-2118436 mesylate) Dacomitinib (PF299804) 2678 5 mg, 25 mg 1110813-31-4 EGFR/ErbB2/ErbB4 BCR-Abl, EGFR, Src, Lck, Yes, EZSolution™ Dasatinib 2029 25 mg 302962-49-8 Fyn, Kit, EphA2, PDGFRβ BCR-Abl, EGFR, Src, Lck, Yes, Dasatinib (BMS-354825, Spryel) 1586 25 mg, 100 mg 302962-49-8 Fyn, Kit, EphA2, PDGFRβ Derazantinib B2222 1 mg, 5 mg 1234356-69-4 FGFR Desmethyl Erlotinib (OSI-420) B2201 1 mg, 5 mg 183320-51-6 EGFR FLT3/c-Kit, FGFR1/3, VEG- Dovintinib Lactate B1615 5 mg, 25 mg 915769-50-5 FR1-4) FLT3/c-Kit, FGFR1/3, VEG- Dovitinib B1614 5 mg, 25 mg 405169-16-6 FR1-4) Dubermatinib (TP-0903) 9590 5 mg, 25 mg 1341200-45-0 AXL Encorafeinb B2103 5 mg, 25 mg 1269440-17-6 B-RafV600E/K Ensartinib B1946 5 mg, 25 mg 1365267-27-1 ALK ROS1+ NSCLC; solid tumors Entrectinib B1324 5 mg, 25 mg 1108743-60-7 with NTRK fusion proteins Erdafitinib B2458 5 mg, 25 mg 1346242-81-6 FGFR1/2/3/4 Erdafitinib B2458 5 mg, 25 mg 1346242-81-6 FGFR1/2/3/4 Erlotinib hydrochloride 1588 100 mg, 1 g 183319-69-9 EGFR Erlotinib, Free base 2048 100 mg, 1 g 183321-74-6 EGFR Evobrutinib B2379 5 mg, 25 mg 1415823-73-2 Bruton’s tyrosine kinase (BTK) Fedratinib (TG101348) 2314 1 mg, 5 mg 936091-26-8 JAK2 EZSolution™ Fedratinib B2487 5 mg 936091-26-8 JAK2 (TG101348) Fenebrutinib (GDC-0853) B2074 5 mg, 25 mg 1434048-34-6 Bruton’s tyrosine kinase (BTK) Foretinib 9476 5 mg, 25 mg 849217-64-7 c-Met and VEGFR2 www.biovision.com www.biovision.com Fostamatinib disodium 1936 1 mg, 5 mg 1025687-58-4 Syk, Spleen tyrosine kinase Fruquintinib B1979 5 mg, 25 mg 1194506-26-7 VEGFR1/2/3 2 Product Name Cat. No. Size CAS. No. Known Targets Gefitinib 1589 5 mg, 25 mg 184475-35-2 EGFR EZSolution™ Gefitinib 2030 5 mg 184475-35-2 EGFR Gilteritinib B1294 5 mg, 25 mg 1254053-43-4 FLT3 Glumetinib B2561 5 mg, 25 mg 1642581-63-2 c-Met Golvatinib 2655 5 mg, 25 mg 928037-13-2 c-Met and VEGFR2 Bruton's tyrosine kinase Ibrutinib (PCI-32675) 2298 5 mg, 25 mg 936563-96-1 (BTK) Icotinib B3003 5mg, 25mg 610798-31-7 EGFR Idealisib (CAL-101) 2613 5 mg, 25 mg 870281-82-6 PI3K catalytic subunit p110δ Imatinib Mesylate (CGP-57148B, 1625 100 mg, 1 g 220127-57-1 BCR-Abl, Kit, PDGFR STI-571) Imatinib, Free base 2141 100 mg, 1 g 152459-95-5 BCR-Abl, Kit, PDGFR Lapatinib Ditosylate 1624 25 mg, 100 mg 388082-78-8 EGFR, ErbB2 EZSolution™ Lapatinib Ditosylate 2807 10 mg 388082-78-8 EGFR, ErbB2 Lapatinib, Free base 2138 25 mg, 100 mg 231277-92-2 EGFR, ErbB2 Larotrectinib (LOXO-101) B2291 5 mg, 25 mg 1223403-58-4 TRKA/B/C Larotrectinib (Sulfate) (LOXO-101 B2545 5 mg, 25 mg 1223405-08-0 TRKA/B/C sulfate) Lazertinib B2348 5 mg, 25 mg 1903008-80-9 EGFR VEGFRs, FGFRs, PDGFR, Kit, Lenvatinib B1157 5 mg, 25 mg 417716-92-8 RET Lestaurtinib 1805 500 µg, 1 mg 111358-88-4 FLT3, JAK2, and TrkA Linifanib (ABT-869) 1615 1 mg, 5 mg 796967-16-3 VEGFR and PDGFR Linsitinib, Free base 2294 5 mg, 25 mg 867160-71-2 IGF-1R and InsR Lorlatinib (PF0643922) B1169 10 mg, 50 mg 1454846-35-5 ALK Masitinib 2007 5 mg, 25 mg 790299-79-5 c-KIT, PDGF and FGFR Merestinib B3007 1mg, 5mg 1206799-15-6 MET Motesanib 2022 5 mg, 25 mg 453562-69-1 VEGFR1/2/3 and PDGFR Motesanib diphosphate B2196 5 mg, 25 mg 857876-30-3 VEGFR1/2/3 and PDGFR Mubritinib (TAK-165) 1961 1 mg, 5 mg 1086062-66-9 PI3-K Naquotinib B1317 5 mg, 25 mg 448232-80-1 EGFR T790M Nazartinib B2288 5 mg, 25 mg 1508250-71-2 EGFR T790M Neratinib 2023 5 mg, 25 mg 698387-09-6 ErbB2/HER2 Nilotinib 1750 25 mg, 100 mg 641571-10-0 BCR-Abl, PDGFR, DDR1 FGFR1/2/3, PDGFRα/β, VEG- Nintedanib (BIBF1120) 2167 5 mg, 25 mg 656247-17-5 FR1/2/3, Flt3 Olmutinib B1218 5 mg, 25 mg 1353550-13-6 EGFR T790M Osimertinib (AZD-9291) 2674 5 mg, 25 mg 1421373-65-0 EGFR T790M EZSolution™ Osimertinib B2490 5 mg 1421373-65-0 EGFR T790M (AZD-9291) Osimertinib (Mesylate) (AZD-9291 B1899 5 mg 1421373-66-1 EGFR T790M Mesylate) Pacritinib (SB1518) 2450 1 mg, 5 mg 937272-79-2 EGFR T790M EZSolution™ Pacritinib (SB1518) B2485 1 mg 937272-79-2 EGFR T790M www.biovision.com VEGFR1/2/3, PDGFRα/β, Pazopanib (GW-786034) 1916 5 mg, 25 mg 444731-52-6 FGFR1/3, Kit, Lck, Fms, Itk Pelitinib (EKB-569) 2676 5 mg, 25 mg 257933-82-7 EGFR 2 3 Product Name Cat. No. Size CAS. No. Known Targets Pexidartinib (PLX-3397) 9617 10 mg, 50 mg 1029044-16-3 CSFR1/Kit Pexmetinib B1711 5 mg, 25 mg 945614-12-0 MAPK and Tie2/Tek BCR-Abl, BCR-Abl T315I, VEGFR, PDGFR, FGFR, EphR, Ponatinib 2712 50 mg, 10 mg 943319-70-8 Src family kinases, Kit, RET, Tie2, Flt3 Poziotinib 9519 10 mg, 50 mg 1092364-38-9 HER1, HER2, and HER4 Quizartinib 2008 1 mg, 5 mg 950769-58-1 FLT3 VEGFR1/2/3, BCR-Abl, B-Raf, Regorafenib 2891 5 mg, 25 mg 755037-03-7 B-Raf(V600E), Kit, PDGFRα/β, RET, FGFR1/2, Tie2, Eph2A VEGFR1/2/3, BCR-Abl, B-Raf, Regorafenib monohydrate B1621 5 mg, 25 mg 1019206-88-2 B-Raf(V600E), Kit, PDGFRα/β, RET, FGFR1/2, Tie2, Eph2A Repotrectinib (TPX-0005) B2027 5 mg, 25 mg 2058227-19-1 ALK Roblitinib B3008 1mg, 5mg 1708971-55-4 FGFR4 Rociletinib (CO-1686) 2794 5 mg, 25 mg 1374640-70-6 EGFRL858R/T790M EZSolution™ Ruxolitinib B2477 5 mg 941678-49-5 JAK1/2 Ruxolitinib Phosphate B2631 5 mg, 25 mg 1092939-17-7 JAK1/2 Ruxolitinib, Free base 2139 5 mg, 25 mg 941678-49-5 JAK1/2 EGFR (ErbB-1), Neu (ErbB-2) Sapitinib (AZD-8931) 9659 5 mg, 25 mg 848942-61-0 and ErbB-3 EZSolution™ Saracatinib B2625 5 mg 379231-04-6 c-Src and Bcr-ABL Saracatinib (AZD-0530) 1582 5 mg, 25 mg 379231-04-6 c-Src and Bcr-ABL Savolitinib B3006 1mg, 5mg 1313725-88-0 c-MET Selpercatinib B2996 1mg, 5mg 2152628-33-4 RET Kinase Semaxanib 9491 5 mg 204005-46-9 VEGFR2 EZSolution™ Semaxanib 9492 5 mg 204005-46-9 VEGFR2 Axl, MER, VEGFR3, VEGFR2, Sitravatinib B2539 5 mg, 25 mg 1123837-84-2 VEGFR1, KIT , FLT3, DDR2, DDR1, TRKA, TRKB B/C-Raf, B-Raf (V600E), Sorafenib (BAY 43-9006), Free 2142 25 mg, 100 mg 284461-73-0 Kit, Flt3, RET, VEGFR1/2/3, base PDGFRβ B/C-Raf, B-Raf (V600E), Sorafenib Tosylate 1594 25 mg, 100 mg 475207-59-1 Kit, Flt3, RET, VEGFR1/2/3, PDGFRβ B/C-Raf, B-Raf (V600E), EZSolution™ Sorafenib(Tosylate) 2031 25 mg 475207-59-1 Kit, Flt3, RET, VEGFR1/2/3, PDGFRβ PDGFRα/β, VEGFR1/2/3, Kit, EZSolution™ Sunitinib Malate 1804 25 mg 341031-54-7 Flt3, CSF-1R, RET 25 mg, 100 mg, PDGFRα/β, VEGFR1/2/3, Kit, Sunitinib, Free base 2097 557795-19-4 1 g Flt3, CSF-1R, RET PDGFRα/β, VEGFR1/2/3, Kit, Sunitinib, Malate (Sutent) 1611 25 mg, 100 mg 341031-54-7 Flt3, CSF-1R, RET Tandutinib 2024 5 mg, 25 mg 387867-13-2 FLT kinase, PDGFRβ and c-Kit EZSolution™ Tandutinib B2627 5 mg 387867-13-2 FLT kinase, PDGFRβ and c-Kit www.biovision.com www.biovision.com 4 Product Name Cat.
Recommended publications
  • Vandetanib-Eluting Beads for the Treatment of Liver Tumours

    Vandetanib-Eluting Beads for the Treatment of Liver Tumours

    VANDETANIB-ELUTING BEADS FOR THE TREATMENT OF LIVER TUMOURS ALICE HAGAN A thesis submitted in partial fulfilment of the requirements for the University of Brighton for the degree of Doctor of Philosophy June 2018 ABSTRACT Drug-eluting bead trans-arterial chemo-embolisation (DEB-TACE) is a minimally invasive interventional treatment for intermediate stage hepatocellular carcinoma (HCC). Drug loaded microspheres, such as DC Bead™ (Biocompatibles UK Ltd) are selectively delivered via catheterisation of the hepatic artery into tumour vasculature. The purpose of DEB-TACE is to physically embolise tumour-feeding vessels, starving the tumour of oxygen and nutrients, whilst releasing drug in a controlled manner. Due to the reduced systemic drug exposure, toxicity is greatly reduced. Embolisation-induced ischaemia is intended to cause tumour necrosis, however surviving hypoxic cells are known to activate hypoxia inducible factor (HIF-1) which leads to the upregulation of several pro-survival and pro-angiogenic pathways. This can lead to tumour revascularisation, recurrence and poor treatment outcomes, providing a rationale for combining anti-angiogenic agents with TACE treatment. Local delivery of these agents via DEBs could provide sustained targeted therapy in combination with embolisation, reducing systemic exposure and therefore toxicity associated with these drugs. This thesis describes for the first time the loading of the DEB DC Bead and the radiopaque DC Bead LUMI™ with the tyrosine kinase inhibitor vandetanib. Vandetanib selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR2) and epidermal growth factor receptor (EGFR), two signalling receptors involved in angiogenesis and HCC pathogenesis. Physicochemical properties of vandetanib loaded beads such as maximum loading capacity, effect on size, radiopacity and drug distribution were evaluated using various analytical techniques.
  • (12) United States Patent (10) Patent No.: US 9,375.433 B2 Dilly Et Al

    (12) United States Patent (10) Patent No.: US 9,375.433 B2 Dilly Et Al

    US009375433B2 (12) United States Patent (10) Patent No.: US 9,375.433 B2 Dilly et al. (45) Date of Patent: *Jun. 28, 2016 (54) MODULATORS OF ANDROGENSYNTHESIS (52) U.S. Cl. CPC ............. A6 IK3I/519 (2013.01); A61 K3I/201 (71) Applicant: Tangent Reprofiling Limited, London (2013.01); A61 K3I/202 (2013.01); A61 K (GB) 31/454 (2013.01); A61K 45/06 (2013.01) (72) Inventors: Suzanne Dilly, Oxfordshire (GB); (58) Field of Classification Search Gregory Stoloff, London (GB); Paul USPC .................................. 514/258,378,379, 560 Taylor, London (GB) See application file for complete search history. (73) Assignee: Tangent Reprofiling Limited, London (56) References Cited (GB) U.S. PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this 5,364,866 A * 1 1/1994 Strupczewski.......... CO7C 45/45 patent is extended or adjusted under 35 514,254.04 U.S.C. 154(b) by 0 days. 5,494.908 A * 2/1996 O’Malley ............. CO7D 261/20 514,228.2 This patent is Subject to a terminal dis 5,776,963 A * 7/1998 Strupczewski.......... CO7C 45/45 claimer. 514,217 6,977.271 B1* 12/2005 Ip ........................... A61K 31, 20 (21) Appl. No.: 14/708,052 514,560 OTHER PUBLICATIONS (22) Filed: May 8, 2015 Calabresi and Chabner (Goodman & Gilman's The Pharmacological (65) Prior Publication Data Basis of Therapeutics, 10th ed., 2001).* US 2015/O238491 A1 Aug. 27, 2015 (Cecil's Textbook of Medicine pp. 1060-1074 published 2000).* Stedman's Medical Dictionary (21st Edition, Published 2000).* Okamoto et al (Journal of Pain and Symptom Management vol.
  • Impact of Toceranib/Piroxicam

    Impact of Toceranib/Piroxicam

    RESEARCH ARTICLE Impact of Toceranib/Piroxicam/ Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi- Institutional Study Cheryl A. London1☯*, Heather L. Gardner1☯, Tamra Mathie1, Nicole Stingle1, Roberta Portela2, Michael L. Pennell3, Craig A. Clifford4, Mona P. Rosenberg5, David M. Vail6, Laurel E. Williams7, Kim L. Cronin8, Heather Wilson-Robles9, Antonella Borgatti10, Carolyn J. Henry11, Dennis B. Bailey12, Jennifer Locke13, Nicole C. Northrup14, Martin Crawford-Jakubiak15, Virginia L. Gill16, Mary K. Klein17, David M. Ruslander18, Doug H. Thamm19, Brenda Phillips20, Gerald Post21 OPEN ACCESS 1 Departments of Veterinary Biosciences and Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America, 2 Department of Veterinary Clinical Citation: London CA, Gardner HL, Mathie T, Stingle Medicine, University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Champaign, Illinois, N, Portela R, Pennell ML, et al. (2015) Impact of United States of America, 3 Division of Biostatistics, College of Public Health, The Ohio State University, Toceranib/Piroxicam/Cyclophosphamide Columbus, Ohio, United States of America, 4 Hope Veterinary Specialists, Malvern, Pennsylvania, United Maintenance Therapy on Outcome of Dogs with States of America, 5 Veterinary Cancer Group, Tustin, California, United States of America, 6 Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Madison, Wisconsin, Appendicular Osteosarcoma following Amputation United States of America, 7 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina and Carboplatin Chemotherapy: A Multi-Institutional State University, Raleigh, North Carolina, United States of America, 8 New England Veterinary Oncology Study. PLoS ONE 10(4): e0124889.
  • The Many Clinical Uses of Palladia

    The Many Clinical Uses of Palladia

    THE MANY CLINICAL USES OF PALLADIA Chad M. Johannes, DVM, DACVIM (SAIM, Oncology) Iowa State University Ames, IA, USA Toceranib phosphate/PALLADIA® (Zoetis) Canine Toceranib phosphate (Palladia®) is a multireceptor tyrosine kinase (RTK) inhibitor approved by the FDA Center for Veterinary Medicine in 2009 for the treatment of dogs with recurrent cutaneous Patnaik grade II or III mast cell tumors. By inhiBiting several memBers of the split-kinase family of RTKs, including vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β), and Kit/stem cell factor receptor (SCFR), toceraniB has both an antiangiogenic as well as direct antitumor role in treating canine mast cell tumors. Palladia has been demonstrated to be effective and well-tolerated in a prospective, placeBo-controlled, multi-center field study in dogs with mast cell tumor.1 There are a number of recent publications to review that help to further define the best clinical use of this powerful therapeutic in various carcinomas and sarcomas in dogs. A. Pulse-dosed Palladia + lomustine for nonresectable canine mast cell tumor (MCT) 2 Lomustine at a dosage of 50 mg/m once every 3 weeks combined with pulse-dosed Palladia was well-tolerated. The oBjective response rate of 46% for this protocol is comparable to what previously has been reported for single-agent protocols, but considerably higher than that reported with single- agent lomustine. ComBining pulse-administered Palladia with lomustine may be a reasonable treatment option for dogs with unresectable or metastatic MCT.2 B. Maintenance Palladia following doxorubicin-based chemotherapy for canine splenic hemangiosarcoma (HSA) Results of this study indicate that use of Palladia following doxorubicin chemotherapy does not improve either DFI or ST in dogs with stage I or II HSA compared to previously puBlished reports of adjuvant chemotherapy for splenic HSA.3 C.
  • Toceranib Phosphate-Associated Nephrotic Syndrome in a Dog: a Case Report Shannon M

    Toceranib Phosphate-Associated Nephrotic Syndrome in a Dog: a Case Report Shannon M

    Remerowski et al. BMC Veterinary Research (2021) 17:146 https://doi.org/10.1186/s12917-021-02850-9 CASE REPORT Open Access Toceranib phosphate-associated nephrotic syndrome in a dog: a case report Shannon M. Remerowski1, Chamisa L. Herrera2 and Lindsay L. Donnelly1* Abstract Background: Nephrotic syndrome (NS) is rare in dogs and is characterized by concurrent clinical findings of proteinuria, hyperlipidemia, hypoalbuminemia, and edema. NS has been reported in humans receiving tyrosine kinase inhibitors (TKI) and in dogs receiving masitinib. This is the first report of NS in a dog receiving toceranib phosphate. Case presentation: An 8-year-old, female, spayed Labrador retriever was diagnosed with a 10 cm mast cell tumor on the left lateral abdomen. After completion of a 12-week vinblastine and prednisone protocol, she began treatment with toceranib phosphate (2.6 mg/kg by mouth, every other day). Proteinuria was documented prior to starting toceranib. On day 426 after diagnosis (day 328 of toceranib phosphate treatment), the dog was evaluated for diarrhea, lethargy and anorexia. On physical examination, dependent edema was noted on the ventral chest and abdomen, and sterile neutrophilic inflammation was aspirated from a 2.3 cm splenic nodule. The following laboratory values were reported: albumin < 1.5 g/dL; cholesterol 378 mg/dl and urine protein to creatinine ratio of 3.79. The patient was diagnosed with NS, and treatment with toceranib phosphate was discontinued. Low-dose aspirin was started in addition to an increased dosage of enalapril (0.47 mg/kg q12hr). No other therapy was instituted. The dog improved clinically, and laboratory values returned to near normal over the 8-week follow-up.
  • Administration of CI-1033, an Irreversible Pan-Erbb Tyrosine

    Administration of CI-1033, an Irreversible Pan-Erbb Tyrosine

    7112 Vol. 10, 7112–7120, November 1, 2004 Clinical Cancer Research Featured Article Administration of CI-1033, an Irreversible Pan-erbB Tyrosine Kinase Inhibitor, Is Feasible on a 7-Day On, 7-Day Off Schedule: A Phase I Pharmacokinetic and Food Effect Study Emiliano Calvo,1 Anthony W. Tolcher,1 sorption and elimination adequately described the pharma- Lisa A. Hammond,1 Amita Patnaik,1 cokinetic disposition. CL/F, apparent volume of distribution ؎ ؎ 1 2 (Vd/F), and ka (mean relative SD) were 280 L/hour ؎Johan S. de Bono, Irene A. Eiseman, ؎ ؊1 2 2 33%, 684 L 20%, and 0.35 hour 69%, respectively. Stephen C. Olson, Peter F. Lenehan, C values were achieved in 2 to 4 hours. Systemic CI-1033 1 3 max Heather McCreery, Patricia LoRusso, and exposure was largely unaffected by administration of a high- 1 Eric K. Rowinsky fat meal. At 250 mg, concentration values exceeded IC50 1Institute for Drug Development, Cancer Therapy and Research values required for prolonged pan-erbB tyrosine kinase in- Center, University of Texas Health Science Center at San Antonio, hibition in preclinical assays. 2 San Antonio, Texas, Pfizer Global Research and Development, Ann Conclusions: The recommended dose on this schedule is Arbor Laboratories, Ann Arbor, Michigan, 3Wayne State University, University Health Center, Detroit, Michigan 250 mg/day. Its tolerability and the biological relevance of concentrations achieved at the maximal tolerated dose war- rant consideration of disease-directed evaluations. This in- ABSTRACT termittent treatment schedule can be used without regard to Purpose: To determine the maximum tolerated dose of meals.
  • Molecular Targets for Anticancer Therapies in Companion Animals and Humans: What Can We Learn from Each Other? Irati Beltrán Hernández1,2*, Jannes Z

    Molecular Targets for Anticancer Therapies in Companion Animals and Humans: What Can We Learn from Each Other? Irati Beltrán Hernández1,2*, Jannes Z

    Theranostics 2021, Vol. 11, Issue 8 3882 Ivyspring International Publisher Theranostics 2021; 11(8): 3882-3897. doi: 10.7150/thno.55760 Review Molecular targets for anticancer therapies in companion animals and humans: what can we learn from each other? Irati Beltrán Hernández1,2*, Jannes Z. Kromhout2*, Erik Teske3, Wim E. Hennink1, Sebastiaan A. van Nimwegen3 and Sabrina Oliveira1,2 1. Pharmaceutics, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, the Netherlands. 2. Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands. 3. Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands. *Equal contributions to this work. Corresponding author: E-mail: [email protected]; Tel.: +31-63-410-3460. © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2020.11.11; Accepted: 2020.12.29; Published: 2021.02.06 Abstract Despite clinical successes in the treatment of some early stage cancers, it is undeniable that novel and innovative approaches are needed to aid in the fight against cancer. Targeted therapies offer the desirable feature of tumor specificity while sparing healthy tissues, thereby minimizing side effects. However, the success rate of translation of these therapies from the preclinical setting to the clinic is dramatically low, highlighting an important point of necessary improvement in the drug development process in the oncology field. The practice of a comparative oncology approach can address some of the current issues, by introducing companion animals with spontaneous tumors in the linear drug development programs.
  • WO 2013/152252 Al 10 October 2013 (10.10.2013) P O P C T

    WO 2013/152252 Al 10 October 2013 (10.10.2013) P O P C T

    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2013/152252 Al 10 October 2013 (10.10.2013) P O P C T (51) International Patent Classification: STEIN, David, M.; 1 Bioscience Park Drive, Farmingdale, Λ 61Κ 38/00 (2006.01) A61K 31/517 (2006.01) NY 11735 (US). MIGLARESE, Mark, R.; 1 Bioscience A61K 39/00 (2006.01) A61K 31/713 (2006.01) Park Drive, Farmingdale, NY 11735 (US). A61K 45/06 (2006.01) A61P 35/00 (2006.01) (74) Agents: STEWART, Alexander, A. et al; 1 Bioscience A61K 31/404 (2006 ) A61P 35/04 (2006.01) Park Drive, Farmingdale, NY 11735 (US). A61K 31/4985 (2006.01) A61K 31/53 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: available): AE, AG, AL, AM, PCT/US2013/035358 kind of national protection AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) International Filing Date: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 5 April 2013 (05.04.2013) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, English (25) Filing Language: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (26) Publication Language: English ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, (30) Priority Data: RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, 61/621,054 6 April 2012 (06.04.2012) US TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (71) Applicant: OSI PHARMACEUTICALS, LLC [US/US]; ZM, ZW.
  • A Combination of Two Receptor Tyrosine Kinase Inhibitors, Canertinib and PHA665752 Compromises Ovarian Cancer Cell Growth in 3D Cell Models

    A Combination of Two Receptor Tyrosine Kinase Inhibitors, Canertinib and PHA665752 Compromises Ovarian Cancer Cell Growth in 3D Cell Models

    Oncol Ther DOI 10.1007/s40487-016-0031-1 ORIGINAL RESEARCH A Combination of Two Receptor Tyrosine Kinase Inhibitors, Canertinib and PHA665752 Compromises Ovarian Cancer Cell Growth in 3D Cell Models Wafaa Hassan . Kenny Chitcholtan . Peter Sykes . Ashley Garrill Received: July 12, 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com ABSTRACT EGFR/Her-2 inhibitor (canertinib) and a c-Met inhibitor (PHA665752) in ovarian cancer cell Introduction: Advanced ovarian cancer is often lines in 3D cell aggregates. a fatal disease as chemotherapeutic drugs have Methods: OVCAR-5 and SKOV-3 ovarian cancer limited effectiveness. Better targeted therapy is cell lines were cultured on a non-adherent needed to improve the survival and quality of surface to produce 3D cell clusters and life for these women. Receptor tyrosine kinases aggregates. Cells were exposed to canertinib including EGFR, Her-2 and c-Met are associated and PHA665752, both individually and in with a poor prognosis in ovarian cancer. combination, for 48 h. The effect on growth, Therefore, the co-activation of these receptors metabolism and the expression/ may be crucial for growth promoting activity. phosphorylation of selective signaling proteins In this study, we explored the effect of associated with EGFR, Her-2 and c-Met were combining two small molecule inhibitors that investigated. target the EGFR/Her-2 and c-Met receptor Results: The single drug treatments tyrosine kinases in two ovarian cancer cell significantly decreased cell growth and altered lines. The aim of this study was to investigate the expression of signaling proteins in the combined inhibition activity of a dual OVCAR-5 and SKOV-3 cell lines.
  • Supporting Information

    Supporting Information

    Supporting Information Lin et al. 10.1073/pnas.1320956111 SI Methods BRAFV600E antibody was purchased from Spring Bioscience. The Cell Lines and Culture Reagents. The HCC364 cell line was kindly anti–β-actin antibody was purchased from Sigma-Aldrich. The anti- provided by David Solit (Memorial Sloan–Kettering Cancer EGFR antibody was purchased from Bethyl Laboratories. Center, New York). H1395, H1755, CAL-12T, H1666, H2405, and H2087 cell lines were purchased from American Type Cul- Plasmids, Transfection, and Viral Infection. Various pBabe–photo- ture Collection. Cells grown in RPMI 1640 supplemented with 10% activated mCherry-tagged BRAF constructs were provided by (vol/vol) FBS, 100 IU/mL penicillin, and 100 μg/mL streptomycin Xiaolin Nan (Oregon Health Sciences University, Portland, OR). were maintained at 37 °C in a humidified atmosphere at 5% CO2. The Flag-tagged or V5-tagged BRAF constructs were cloned using The HCC364 vemurafenib-resistant sublines VR1–VR5 were the Gateway system (Invitrogen). EGFR shRNAs were purchased maintained in the above medium and 5 μmol/L of vemurafenib. from Sigma-Aldrich. All transient transfections were conducted using Fugene 6 (Promega). For retroviral infection, viruses were Compounds. Vemurarenib, dabrafenib, AZD6244, gefitinib, and produced in 293-GPG cells. For lentiviral infection, viruses were afatinib were purchased from Sellekchem. Erlotinib was pur- produced in HEK293FT cells cotransfected with packaging re- chased from LC Laboratories. agents ViraPower (Invitrogen). Whole-Exome Sequencing. DNA from each of the indicated lines siRNA-Mediated Gene Silencing. siRNAs against EGFR and c-Jun was extracted using the QIAamp DNA mini kit (Qiagen). DNA were purchased from Dharmacon.
  • Small-Molecule Inhibitors of the Receptor Tyrosine Kinases: Promising Tools for Targeted Cancer Therapies

    Small-Molecule Inhibitors of the Receptor Tyrosine Kinases: Promising Tools for Targeted Cancer Therapies

    Int. J. Mol. Sci. 2014, 15, 13768-13801; doi:10.3390/ijms150813768 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Review Small-Molecule Inhibitors of the Receptor Tyrosine Kinases: Promising Tools for Targeted Cancer Therapies Mohammad Hojjat-Farsangi Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm 17176, Sweden; E-Mail: [email protected]; Tel.: +46-517-74308; Fax: +46-517-75897 Received: 3 July 2014; in revised form: 31 July 2014 / Accepted: 5 August 2014 / Published: 8 August 2014 Abstract: Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK–TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK–TKIs have been developed for the treatment of cancer patients. Specific/selective RTK–TKIs have shown less deleterious effects compared to multi-targeted inhibitors.
  • Detection of Tyrosine Kinase Inhibitors-Induced COX-2 Expression in Bladder Cancer by Fluorocoxib A

    Detection of Tyrosine Kinase Inhibitors-Induced COX-2 Expression in Bladder Cancer by Fluorocoxib A

    www.oncotarget.com Oncotarget, 2019, Vol. 10, (No. 50), pp: 5168-5180 Research Paper Detection of tyrosine kinase inhibitors-induced COX-2 expression in bladder cancer by fluorocoxib A Jennifer Bourn1,2,4, Sony Pandey1, Jashim Uddin3, Lawrence Marnett3 and Maria Cekanova1,2 1Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37996, USA 2University of Tennessee and Oak Ridge National Laboratory, Graduate School of Genome Science and Technology, The University of Tennessee, Knoxville, TN 37996, USA 3A. B. Hancock, Jr., Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry and Pharmacology, Vanderbilt Institute of Chemical Biology, Center for Molecular Toxicology and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA 4Current address: Department of Cancer Biology, College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA Correspondence to: Maria Cekanova, email: [email protected] Keywords: bladder cancer; TKIs; RTKIs; COX-2; targeted therapies Received: June 18, 2019 Accepted: July 17, 2019 Published: August 27, 2019 Copyright: Bourn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Among challenges of targeted therapies is the activation of alternative pro- survival signaling pathways in cancer cells, resulting in an acquired drug resistance. Cyclooxygenase-2 (COX-2) is overexpressed in bladder cancer cells, making it an attractive molecular target for the detection and treatment of cancer. Fluorocoxib A is an optical imaging agent that selectively targets COX-2.